Crystal growth control is essential in various fields of science and technology (e.g., chemistry, materials science, pharmaceutical development). For instance, changes in the size and shape of crystals of pharmaceutical compounds can impact their bioavailability, chemical stability, and production efficiency. Traditional methods to control crystallization usually include the alterations of temperature, solvent, supersaturation, and seeding conditions. A number of recent methods, such as using tailor-made additives, ledge-directed epitaxy, polymer microgel, polymer heteronuclei, capillaries, porous materials, and laser-induced nucleation have been developed and employed in the crystallization process of certain compounds to select favored and/or discover new crystalline forms of the compounds.
The concept of molecular recognition has been successfully used to elucidate the effects of additives (foreign ions or molecules) on crystal growth. Peptides and proteins are often used in vivo and in vitro to control the growth of minerals and produce new forms of solids with different physicochemical properties. For example, peptide additives in either α-helix or β-sheet arrangement designed to interact with calcite crystal faces have been demonstrated to control calcite crystal habit. Size and shape control of organic crystals, however, is more difficult due to their anisotropic properties (different atomic arrangements in three dimensions).
Although tremendous effort has been devoted to understanding the crystallization process and selective crystallization, the crystallization control process remains largely trial-and-error, experiencing substantial difficulties in exclusive production of the desired forms as well as the production of both thermodynamically and kinetically less favored forms. Moreover, much less progress has been made in additive-controlled organic crystallization than in additive-controlled inorganic crystallization, and the selective production of organic single crystals with defined crystal phase and morphology still remains an enigma. For example, nucleosides and their analogues, an important class of pharmaceutical compounds, have been used as viral mutagens, drugs for induction therapy, effective treatment of lymphoproliferative disorders, and spinal cord injury, however little is known about their size and shape control using additives.
Antifreeze polypeptides (AFPs) are a structurally diverse group of proteins found in many cold-adapted organisms to protect them from freeze damage through a noncolligative manner, providing an intriguing example of ice crystal growth control. AFPs can bind to specific faces of ice crystals and modify the habit of the ice crystals. Their affinity to ice depends on hydrogen bonding and hydrophobic interactions, unlike most protein-mineral interactions where ionic interactions often play a dominant role. Ice and clathrate hydrates (ice-like crystalline solids) are known to be inhibited and modified by AFPs. Although ice is known with many polymorphs, studies on ice morphs induced by AFPs are lacking. Until now, AFP studies focused on the isolation, antifreeze activity, structure determination, and ice or ice-like solid binding of AFPs. Detailed mechanisms of AFPs still remain unknown.